阿魏酸川芎嗪固体脂质纳米粒制备及处方工艺优化

Preparation technology research of ferulic acid Ligustrazine solid lipid nanoparticles

目的:制备阿魏酸川芎嗪(FATM)固体脂质纳米粒(SLN),并优化其处方。方法:本课题采用乳化-超声法制备阿魏酸川芎嗪固体脂质纳米粒(FATM-SLN),以包封率为考察指标,以单硬脂酸甘油酯、蛋黄卵磷脂(PC)、泊洛沙姆188(F68)、硬脂酸钠为考察因素,通过单因素实验和正交实验优化处方及工艺,并按照最优工艺制备FATM-SLN,进行验证实验。结果:最优处方:阿魏酸川芎嗪(10 mg),单硬脂酸甘油酯(300 mg),乙酸丁酯(1.5 mL),PC(400 mg),F68(400mg),硬脂酸钠(10 mg),纯化水(20 mL)。最优工艺条件:水相(硬脂酸钠、F68、纯化水),油相(主药、单硬脂酸甘油酯、PC、乙酸丁酯)。验证实验结果:FATM-SLN质量浓度0.35 mg/mL,外观形态圆整,粒径在100～200 nm,平均粒径105.3nm,Zeta电位-34.8 mV,4℃放置10 d稳定性良好,FATM-SLN在0.5～1 h释放最快,1 h释放量达到60.47%,8 h以后趋于平稳,药物基本释放完全。结论:本研究通过正交设计筛选优化处方工艺,制备了粒径小,包封率高、稳定性好的阿魏酸川芎嗪固体脂质纳米粒。

OBJECTIVE: To preparate Ligustrazine Ferulate(FATM) solid lipid nanoparticles(SLN) and optimize its prescription. METHODS: The solid lipid nanoparticles(FATM-SLN) were preparated by emulsification ultrasonic method, and the encapsulation efficiency were used as the investigation indexes. Glycerol monostearate, egg yolk lecithin(PC), poloxamer 188(F68), sodium stearate were used as investigation factors. Through single factor experiment and orthogonal experiment to optimize the formulation and process. According to the optimal process to prepare FATM-SLN and verified experimentally. RESULTS: The best prescription: the main drugs(10 mg), single stearic acid glycerol ester(300 mg), butyl acetate(1.5 mL), PC(400 mg), F68(400 mg),stearic acid(10 mg), purified water(20 mL). The optimal process conditions: aqueous phase(stearic acid sodium, F68, purified water,oil phase(main drug and single stearic acid glyceride, PC, butyl acetate). Verify experimental results: the concentration of FATMSLN was 0.35 mg/mL, the appearance shape was round, particle size range was 100～200 nm, average particle size was 105.3 nm,Zeta potential was-34.8 mV, has stable performance at 4. FATM-SLN release in 0.5～1 h was the fastest, 1 h release reached to60.47%, after 8 h smooth and the drug release completely. CONCLUSION: The solid lipid nanoparticles with small particle size and high encapsulation efficiency were prepared by orthogonal design.